Fan Ruo-Ying, Gao Ru-Meng, Li Jia-Shang, Su Shu-Lan, Shang Er-Xin, Qian Da-Wei, Duan Jin-Ao
Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing, China.
Curr Drug Metab. 2023;24(6):434-447. doi: 10.2174/1389200224666230808090614.
3-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) are the main active components of frankincense as pentacyclic triterpenoids, which are designated by the European Pharmacopoeia 8.0 as the quality standard for the evaluation of Indian frankincense, 2-methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (MCS134) is a non-volatile sesquiterpene compound in myrrh.
In this paper, the absorption pharmacokinetics and metabolites of AKBA, KBA and MCS134 after frankincense, myrrh and their compatibility were analyzed, elaborated their absorption and metabolism mechanism and provided the ideas for the research on the bioactive components of frankincense and myrrh compatibility .
The area under the blood concentration time curve (AUC), half-life (t1/2) and drug clearance (CL) of AKBA, KBA and MCS134 in rats were analyzed by LC-TQ / MS. The metabolites of AKBA, KBA and MCS134 in rats were analyzed by ultra-high pressure liquid chromatography with a linear ion trap-high resolution Orbitrap mass spectrometry system (UHPLC-LTQ-Orbitrap-MS).
The results showed that AKBA, KBA and MCS134 reached the maximum plasma concentration at about 2 h, 2 h and 15 min, respectively. AUC0-t and t1/2 of the three components increased in varying degrees after compatibility, and the clearance/ bioavailability (CL/F) decreased. AKBA, KBA and MCS134 were metabolized in phase I and phase II in rats, and there represented differences before and after compatibility.
After the compatibility of frankincense and myrrh, the absorption of effective components was improved to some extent, and there were some differences in the metabolites in rats. The results provide ideas for elucidating the effect mechanism of frankincense and myrrh.
3-乙酰基-11-酮基-β-乳香酸(AKBA)和11-酮基-乳香酸(KBA)是乳香的主要活性成分,属于五环三萜类化合物,欧洲药典8.0将其指定为评价印度乳香的质量标准,2-甲氧基-8,12-环氧吉马烷-1(10),7,11-三烯-6-酮(MCS134)是没药中的一种非挥发性倍半萜化合物。
分析乳香、没药及其配伍后AKBA、KBA和MCS134的吸收药代动力学及代谢产物,阐述其吸收和代谢机制,为乳香没药配伍活性成分的研究提供思路。
采用LC-TQ / MS分析大鼠体内AKBA、KBA和MCS134的血药浓度-时间曲线下面积(AUC)、半衰期(t1/2)和药物清除率(CL)。采用超高压液相色谱-线性离子阱-高分辨轨道阱质谱系统(UHPLC-LTQ-Orbitrap-MS)分析大鼠体内AKBA、KBA和MCS134的代谢产物。
结果显示,AKBA、KBA和MCS134分别在约2小时、2小时和15分钟时达到最大血药浓度。配伍后三种成分的AUC0-t和t1/2均有不同程度升高,清除率/生物利用度(CL/F)降低。AKBA、KBA和MCS134在大鼠体内经历I相和II相代谢,且配伍前后存在差异。
乳香与没药配伍后,有效成分的吸收有一定程度提高,大鼠体内代谢产物存在一些差异。该结果为阐明乳香与没药的作用机制提供了思路。